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Heme cytotoxicity is the consequence of endoplasmic reticulum stress in atherosclerotic plaque progression
Hemorrhage and hemolysis with subsequent heme release are implicated in many pathologies. Endothelial cells (ECs) encounter large amount of free heme after hemolysis and are at risk of damage from exogenous heme. Here we show that hemorrhage aggravates endoplasmic reticulum (ER) stress in human caro...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129109/ https://www.ncbi.nlm.nih.gov/pubmed/34001932 http://dx.doi.org/10.1038/s41598-021-89713-3 |
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author | Pethő, Dávid Hendrik, Zoltán Nagy, Annamária Beke, Lívia Patsalos, Andreas Nagy, László Póliska, Szilárd Méhes, Gábor Tóth, Csaba Potor, László Eaton, John W. Jacob, Harry S. Balla, György Balla, József Gáll, Tamás |
author_facet | Pethő, Dávid Hendrik, Zoltán Nagy, Annamária Beke, Lívia Patsalos, Andreas Nagy, László Póliska, Szilárd Méhes, Gábor Tóth, Csaba Potor, László Eaton, John W. Jacob, Harry S. Balla, György Balla, József Gáll, Tamás |
author_sort | Pethő, Dávid |
collection | PubMed |
description | Hemorrhage and hemolysis with subsequent heme release are implicated in many pathologies. Endothelial cells (ECs) encounter large amount of free heme after hemolysis and are at risk of damage from exogenous heme. Here we show that hemorrhage aggravates endoplasmic reticulum (ER) stress in human carotid artery plaques compared to healthy controls or atheromas without hemorrhage as demonstrated by RNA sequencing and immunohistochemistry. In EC cultures, heme also induces ER stress. In contrast, if cultured ECs are pulsed with heme arginate, cells become resistant to heme-induced ER (HIER) stress that is associated with heme oxygenase-1 (HO-1) and ferritin induction. Knocking down HO-1, HO-2, biliverdin reductase, and ferritin show that HO-1 is the ultimate cytoprotectant in acute HIER stress. Carbon monoxide-releasing molecules (CORMs) but not bilirubin protects cultured ECs from HIER stress via HO-1 induction, at least in part. Knocking down HO-1 aggravates heme-induced cell death that cannot be counterbalanced with any known cell death inhibitors. We conclude that endothelium and perhaps other cell types can be protected from HIER stress by induction of HO-1, and heme-induced cell death occurs via HIER stress that is potentially involved in the pathogenesis of diverse pathologies with hemolysis and hemorrhage including atherosclerosis. |
format | Online Article Text |
id | pubmed-8129109 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81291092021-05-19 Heme cytotoxicity is the consequence of endoplasmic reticulum stress in atherosclerotic plaque progression Pethő, Dávid Hendrik, Zoltán Nagy, Annamária Beke, Lívia Patsalos, Andreas Nagy, László Póliska, Szilárd Méhes, Gábor Tóth, Csaba Potor, László Eaton, John W. Jacob, Harry S. Balla, György Balla, József Gáll, Tamás Sci Rep Article Hemorrhage and hemolysis with subsequent heme release are implicated in many pathologies. Endothelial cells (ECs) encounter large amount of free heme after hemolysis and are at risk of damage from exogenous heme. Here we show that hemorrhage aggravates endoplasmic reticulum (ER) stress in human carotid artery plaques compared to healthy controls or atheromas without hemorrhage as demonstrated by RNA sequencing and immunohistochemistry. In EC cultures, heme also induces ER stress. In contrast, if cultured ECs are pulsed with heme arginate, cells become resistant to heme-induced ER (HIER) stress that is associated with heme oxygenase-1 (HO-1) and ferritin induction. Knocking down HO-1, HO-2, biliverdin reductase, and ferritin show that HO-1 is the ultimate cytoprotectant in acute HIER stress. Carbon monoxide-releasing molecules (CORMs) but not bilirubin protects cultured ECs from HIER stress via HO-1 induction, at least in part. Knocking down HO-1 aggravates heme-induced cell death that cannot be counterbalanced with any known cell death inhibitors. We conclude that endothelium and perhaps other cell types can be protected from HIER stress by induction of HO-1, and heme-induced cell death occurs via HIER stress that is potentially involved in the pathogenesis of diverse pathologies with hemolysis and hemorrhage including atherosclerosis. Nature Publishing Group UK 2021-05-17 /pmc/articles/PMC8129109/ /pubmed/34001932 http://dx.doi.org/10.1038/s41598-021-89713-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Pethő, Dávid Hendrik, Zoltán Nagy, Annamária Beke, Lívia Patsalos, Andreas Nagy, László Póliska, Szilárd Méhes, Gábor Tóth, Csaba Potor, László Eaton, John W. Jacob, Harry S. Balla, György Balla, József Gáll, Tamás Heme cytotoxicity is the consequence of endoplasmic reticulum stress in atherosclerotic plaque progression |
title | Heme cytotoxicity is the consequence of endoplasmic reticulum stress in atherosclerotic plaque progression |
title_full | Heme cytotoxicity is the consequence of endoplasmic reticulum stress in atherosclerotic plaque progression |
title_fullStr | Heme cytotoxicity is the consequence of endoplasmic reticulum stress in atherosclerotic plaque progression |
title_full_unstemmed | Heme cytotoxicity is the consequence of endoplasmic reticulum stress in atherosclerotic plaque progression |
title_short | Heme cytotoxicity is the consequence of endoplasmic reticulum stress in atherosclerotic plaque progression |
title_sort | heme cytotoxicity is the consequence of endoplasmic reticulum stress in atherosclerotic plaque progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129109/ https://www.ncbi.nlm.nih.gov/pubmed/34001932 http://dx.doi.org/10.1038/s41598-021-89713-3 |
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